3D-QSAR Studies on Thiazolidin-4-one S1P1 Receptor Agonists by CoMFA and CoMSIA

Abstract

Selective S1P1 receptor agonists have therapeutic potential to treat a variety of immune-mediated diseases. A series of 2-imino-thiazolidin-4-one derivatives displaying potent S1P1 receptor agonistic activity were selected to establish 3D-QSAR models using CoMFA and CoMSIA methods. Internal and external cross-validation techniques were investigated as well as some measures including region focusing, progressive scrambling, bootstraping and leave-group-out. The satisfactory CoMFA model predicted a q2 value of 0.751 and an r2 value of 0.973, indicating that electrostatic and steric properties play a significant role in potency. The best CoMSIA model, based on a combination of steric, electrostatic, hydrophobic and H-bond donor descriptors, predicted a q2 value of 0.739 and an r2 value of 0.923. The models were graphically interpreted using contour plots which gave more insight into the structural requirements for increasing the activity of a compound, providing a solid basis for future rational design of more active S1P1 receptor agonists.

Design and Screening of New Lead Compounds for Autism Based on QSAR Model and Molecular Docking Studies

“…The parameter determines the extent of the range of predicted affinity values for the whole dataset and the observed affinity. Those values above including and should be higher than 0.5 for a satisfactory model [ 19 , 20 ].…”

Quantitative Structure-Activity Relationship Studies on Indenoisoquinoline Topoisomerase I Inhibitors as Anticancer Agents in Human Renal Cell Carcinoma Cell Line SN12C

“…are given in Tables 4 , 5 . For convenience, we have converted the cytotoxicity GI50 values of topoisomerase inhibitors in renal carcinoma cell line SN12C to their negative logarithm (pGI50) values, which have a span of 4.0 log units from 4.00 to 8.00, providing a broad and homogeneous data set for 3D-QSAR study (see Table 5 ) [ 24 , 25 ]. Seven compounds were randomly selected as the test set, based on the structural and active diversities with the remaining 41 compounds as the training set.…”